Positive Effects of Physical Activity on Insulin Signaling

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Małkowska comprehensively review the effect of physical activity to improve insulin signaling.

I would like to address following points:

·         The improvement on the title is advisable. „Effects of physical activity on mechanism of insulin resistance” may lead to the misunderstanding, that physical activity contributes to the insulin resistance.

·         Line 76-78, author wrote „Exercise stimulates the translocation of glucose transporter proteins (GLUT4) to the cell membrane, facilitating glucose uptake into muscle cells independently of insulin [12–14].”  In the 3 references provided, the results or conclusion that support the author”s statement that exercie can stimulate GLUT4 to cell membrane and facilitate glucose uptake into muscle cells independently of insulin could not be found. Author needs to elaborate on this point because GLUT4 translocation is insulin-dependent.

·         Figure legends need major improvements to highlight important points illustrated in the figure.

·         Line 133-138, author wrote „Skeletal muscle is a highly energetically demanding tissue, requiring substantial resources to function efficiently. The energy stored within muscle cells is predominantly reserved for future needs. However, there is an exception with the 3-carbon molecules, such as lactate and alanine, which are products of glycolysis. These molecules are synthesized within skeletal muscle and are primarily transported to the liver, serving as substrates for further metabolic processes [1].”. Author cited and rephrased reference [1] for this statement. However, this sentence may be misleading. Alanine can be formed from pyruvate and glutamate catalyzed by alanine aminotransferase, but not a product of glycolysis. Author may give explanation for this point.

·         Line 179: In vivo, white adipocytes exhibit high sensitivity to insulin. Please provide reference for this statement.

·         Line 311-312: Adipose tissue, particularly visceral adipose tissue, serves as a major source of pro-inflammatory cytokines in obesity. Please provide relevant references for this.

·         Include the references for content in Table 1.

·         Remove black box in line 241.

·          The title of this review is „Effects of physical activity on mechanism of insulin resistance”. However, author included insulin signaling in WAT and liver and physical activity was not correlated in those sections (section 2.2 and 2.3). Author may be required to connect those sections to the physical activity. In addition, the similar point goes to secrion 3. Author may connect mitochondrial dysfunction, oxidative stress, ER stress, and lipid accumulation with physical activity: combining section 3 and 4 to make it more compact and comprehensive.

Comments on the Quality of English Language

English is fine, moderate editing is required.

Please pay attention to the nomenclature of protein or gene (human or mice).

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The authors´ narrative review aimed to document the health promoting benefits of physical activity (any kind; at physiological, cellular, and molecular levels) on insulin resistance (IR). The manuscript is organized in two parts: A) Relevant physiological/molecular features of IR [Lines 26-68 (introduction) and 101-448 (body of text), 73%] and B) Effect of physical activity (any kind, not specified) on IR at the same levels [Lines 69-100 (Introduction), 449-560 (body of text), 27%). Two figures (supporting information in section A) were included and the manuscript´s narrative was supported by mostly old references [56% (81) of all references (145) are ≥10 y old]. Important references on this field were not included (doi: 10.1136/bmjsem-2016-000143 , 10.4172/2F2165-7904.S5-003 , 10.1542/peds.2013-2718 , 10.1002/dmrr.2488 ). This update on the topic could be relevant and unique if you consider doing the following:

General. A) Use Italics when needed (e.g. in vivo, line 179). B) Once the manuscript is modified, have it reviewed by a native English speaker. C) Reduce plagiarism (Currently 23%; see iThethicate report).  

Title/Abstract. OK.  

Introduction.  A) Seems quite long, certain statements should be used to feed the body of text (section 2 onwards). B) Add a graphical abstract (Factors to be addressed in each section of the narrative review).

Body of text. A) The authors should favor the topic of the effect of physical activity/exercise on IR (types, intensity, acute and chronic effect, physiological factors associated with the severity/stage of IR) and reduce what refers to the generalities of IR, at a 50/50% ratio at least.

B) Do not forget to highlight, when appropriate, the scientific contribution of this study

Tables & Figures. A) Should be formatted and provided with enough resolution as requested by this journal. B) Be sure to include the explanation of each of them as footnotes, so that their understanding is independent of the text. C) Authors should consider including a systematic review analysis (Table) on the benefits of physical activity (include information of type of exercising, protocol, etc.) on key molecular markers related to IR

References. A) Authors should improve the ratio of new-to-old references to say 75:25. B) Review once again their format according to authors ‘guidelines. C) Authors should consider adding the aforementioned articles (or similar narrative/systematic reviews) to strengthening evidence.

Comments on the Quality of English Language

Moderate changes are needed

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for accepting most of my comments, the manuscript improved significantly.

Comments on the Quality of English Language

Minor editing is needed